The broad objectives of the proposed research are to provide experimental evidence to elucidate the biochemical and hormonal control mechanisms by which mammalian adipocytes regulate the rate of glucose uptake and conversion into its major metabolic products, CO2, glyceride-glycerol and glyceride-fatty acids. The role of the intracellular free fatty acids, intermediate products of lipolysis, in their capacity to influence the rate and pattern of glucose metabolism and the adipocyte responsiveness to insulin will be assessed. The studies will be conducted with isolated adipose cells, varying in mean diameter and volume, removed from subjects of four different species with varying degrees of adiposity. Investigations will include the following objectives: Topic 1) To elucidate regulatory mechanisms of glucose transport and metabolism at the cellular level; Topic 2) To study the responsiveness of adipocytes to hormonal stimuli on the lipolytic and lipogenic processes; and Topic 3) To determine the influence of aging, obesity and exercise on adipocyte functions and hormonal responsiveness. The approach outlined in this application takes advantage of techniques developed to study simultaneously a multiplicity of metabolic parameters and their interrelationships in cell samples of well characterized isolated fat cell populations. The ultimate goal of the applicant's research is to elucidate the metabolic functions of the human adipocytes and the influences upon them of variables (such as aging, obesity, nutritional state, exercise, etc.), which can be better investigated at first in subhuman animal species.